1,3,6-trimethyl-5-aminouracil | 55276-24-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,3,6-trimethyl-5-aminouracil
• 英文别名: 5 amino-1,3,6 trimethyluracil；5-amino-1,3,6-trimethyluracil；ATMU；5-amino-1,3,6-dimethyl-1H-pyrimidine-2,4-dione；5-amino-1,3,6-trimethyl-1H-pyrimidine-2,4-dione；5-Amino-1,3,6-trimethyl-1H-pyrimidin-2,4-dion；5-Amino-1,3,6-trimethylpyrimidine-2,4-dione
• CAS: 55276-24-9
• 化学式: C₇H₁₁N₃O₂
• mdl: MFCD00092009
• 分子量: 169.183
• InChiKey: FDKLGFYAEDLCNA-UHFFFAOYSA-N

物化性质

• 熔点：
  165-166 °C
• 沸点：
  254.3±43.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  66.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3,6-trimethyl-5-aminouracil 在 N,N-二甲基甲酰胺二甲基缩醛 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 6-((E)-2-Dimethylamino-vinyl)-5-{[1-(4-methoxy-phenyl)-meth-(E)-ylidene]-amino}-1,3-dimethyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Senga, Keitaro; Fukami, Kiyoko; Kanazawa, Hashime, Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 805 - 808

  摘要：

  DOI：
• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 盐酸 、 硝酸 、 phosphorus pentoxide 、 tin(ll) chloride 作用下， 生成 1,3,6-trimethyl-5-aminouracil
  参考文献：
  名称：

  Senda; Suzui, Chemical and pharmaceutical bulletin, 1958, vol. 6, p. 476,478

  摘要：

  DOI：

文献信息

• [EN] FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS<br/>[FR] DÉRIVÉS DE PYRIMIDINEDIONES FUSIONNÉS UTILISÉS COMME MODULATEURS DES RÉCEPTEURS TRPA1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2010109287A1

  公开（公告）日：2010-09-30

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPAl (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPAl. Formula (I)

  本发明描述的是一类新颖的杂合吡啶二酮衍生物，其化学公式为（I），这些衍生物是TRPA（瞬时受体电位亚家族A）的调节剂。特别是，本文所述的化合物对于治疗或预防由TRPA1（瞬时受体电位亚家族A成员1）调控的疾病、状况和/或失调是有用的。本发明还提供了制备所述化合物、它们合成中使用的中间体、药物组合物以及治疗或预防由TRPA1调控的疾病、状况和/或失调的方法。公式（I）
• Effect of the 6-Methyl Group on Peroxyl Radical Trapping by 5-Hydroxyand 5-Amino- Derivatives of 1,3-Dimethyluracil
  作者：Stanislav Grabovskiy、Arcadiy Antipin、Yulia Grabovskaya、Nadezhda Andriayshina、Oksana Akchurina、Natalie Kabal'nova

  DOI：10.2174/1570178614666161121123024

  日期：2017.2.13

  Background: Many synthetic and natural uracil derivatives have biological activity. Furthermore, many of these derivatives have pro- and antioxidant properties, but the mechanism of these processes is far from being understood. Methods: Oxygen-uptake kinetics and computational methods (CBS-QB3, M062X/MG3S and SMDM05/ MG3S) were combined to study the reaction of peroxyl radicals with five organic-soluble derivatives: 5-amino- and 5-hydroxy-1,3-dimethyluracil, 5-amino- and 5-hydroxy-1,3,6-trimethyluracil, and 5-hydroxy-1,3-dimethyl-6-phenyluracil in chlorobenzene. Results: The studied uracil derivatives should be classified as inhibitors of medium reactivity kin = (1-10) × 10-4 M-1 s-1. The methyl group in the 6-position of the pyrimidine ring increases the rate constant of the reaction with peroxyl radicals by 3-4 times and the stoichiometric coefficient of inhibition. The calculation of the reaction barrier heights at the SMD-M05/MG3S level of theory for the hydrogen abstraction is in good agreement with experimental data. Conclusion: 1,3-Dimethyl-5-aminouracil is transformed by the addition of a methyl group at the 6-position into a favic-like pyrimidine, while the 5-hydroxy derivative becomes a more effective antioxidant. The bound dissociation energy (O-H or N-H) and the IP for the reactivity forecasting of uracil derivatives were used, but it was found that this methodology did not lead to good correlation between experimental and theoretical results. The SMD-M05/MG3S method provided the most accurate calculations of the reaction barrier heights for hydrogen abstraction from uracil derivatives by peroxyl radical.

  背景：许多合成和天然的尿嘧啶衍生物具有生物活性。此外，这些衍生物中的许多具有促进氧化和抗氧化特性，但其作用机制远未被理解。 方法：结合氧摄取动力学和计算方法（CBS-QB3、M062X/MG3S 和 SMDM05/MG3S）研究了过氧自由基与五种有机可溶性衍生物的反应：5-氨基和5-羟基-1,3-二甲基尿嘧啶、5-氨基和5-羟基-1,3,6-三甲基尿嘧啶，以及5-羟基-1,3-二甲基-6-苯基尿嘧啶在氯苯中的反应。 结果：所研究的尿嘧啶衍生物应归类为中等反应活性抑制剂，反应速率常数kin = (1-10) × 10-4 M-1 s-1。嘧啶环的6位甲基增加了与过氧自由基反应的速率常数3-4倍，并增加了抑制的化学计量系数。在SMD-M05/MG3S理论水平上对氢抽提反应势垒高度的计算与实验数据吻合良好。 结论：1,3-二甲基-5-氨基尿嘧啶通过在6位添加一个甲基，转化为类似favic的嘧啶，而5-羟基衍生物则成为更有效的抗氧化剂。使用了结合解离能（O-H或N-H）和IP来进行尿嘧啶衍生物反应性的预测，但发现这种方法并未导致实验和理论结果之间的良好相关性。SMD-M05/MG3S方法为过氧自由基从尿嘧啶衍生物中抽提氢的反应提供了最准确的势垒高度计算。
• A facile conversion of the methyl group to the cyano group of 5-amino-6-methyluracils and 4-aminoantipyrine
  作者：Taisei Ueda、Hisatomo Yoshida、Jinsaku Sakakibara

  DOI：10.1016/s0040-4039(00)96569-9

  日期：1987.1

  A facile conversion of the methyl group of 1,3-disubstituted 5-amino-6-methyluracils (1a-c) or 4-amino-antipyrine (5) to a cyano group was carried out via fused isoselenazole ring-formation followed by nitration and reduction.

  通过稠合的异戊烯唑环形成，然后硝化，将1,3-二取代的5-氨基-6-甲基尿嘧啶（1a-c）或4-氨基-安替比林（5）的甲基轻松转化为氰基和减少。
• Cardioactive aryloxypropanolamines
  申请人：Boehringer Mannheim GmbH

  公开号：US04438128A1

  公开（公告）日：1984-03-20

  The present invention provides aryloxypropanolamines of the general formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are hydrogen or halogen atoms or lower alkyl, cyano, carboxamido, hydroxyl, lower acyloxy, lower alkoxy, lower alkenyloxy or aryl lower alkoxy radicals, R.sub.5 and R.sub.6, which may be the same or different, are hydrogen atoms or lower alkyl radicals, X is a straight or branched alkylene chain containing 2 to 6 carbon atoms, A is a mono-, bi- or tricyclic heteroaromatic or hydroheteroaromatic radical or, when at least one of the symbols R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is other than a hydrogen atom, may also be a phenyl radical, with the proviso that when A is a uracil-6-yl radical, the 5-position of the uracil moiety does not contain a hydrogen atom, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11, which may be the same or different, are mono- or divalent substituents selected from hydrogen, halogen, nitro, hydroxylamino, amino, lower acylamino, lower alkylamino, di-(lower alkyl)-amino, hydroxyethylamino, di-(hydroxyethyl)-amino, hydroxyl, lower alkoxy, allyloxy, methoxy lower alkoxy, cyano, carboxamido, carboxy, lower alkoxycarbonyl, hydroxymethyl, lower alkoxymethyl, halomethyl, aminomethyl, lower acylaminomethyl, di-(lower alkyl)-aminomethyl, pyrrolidinomethyl, piperidinomethyl, di-(hydroxyethyl)-aminomethyl, morpholinomethyl, piperazinomethyl, 4-lower acylpiperazinomethyl, 4-lower alkylpiperazinomethyl, lower alkyl, lower alkenyl, 2-cyanoethyl, 2-(lower alkoxycarbonyl)-ethyl, 2-carboxyethyl, 2-hydroxyethyl, phenyl lower alkyl and phenyl, the phenyl radicals being optionally substituted with 1 or 2 hydroxyl or methoxy radicals, or from oxygen or sulphur; the optically-active forms and the racemic mixtures thereof, and the pharmacologically compatible salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them.

  本发明提供了一般式为：##STR1##的芳氧基丙醇胺，其中R.sub.1、R.sub.2、R.sub.3和R.sub.4，可能相同或不同，是氢或卤素原子或低碳基、氰基、羧酰胺基、羟基、低酰氧基、低烷氧基、低烯氧基或芳基低烷氧基基团，R.sub.5和R.sub.6，可能相同或不同，是氢原子或低碳基基团，X是直链或支链烷基链，含有2至6个碳原子，A是单环、双环或三环杂芳基或羟杂芳基基团，或者当R.sub.1、R.sub.2、R.sub.3和R.sub.4中至少有一个不是氢原子时，也可以是苯基基团，但是当A是尿嘧啶-6-基团时，尿嘧啶基团的5位不含氢原子，R.sub.7、R.sub.8、R.sub.9、R.sub.10和R.sub.11，可能相同或不同，是来自氢、卤素、硝基、羟胺基、氨基、低酰胺基、低烷基氨基、二-(低烷基)-氨基、羟乙基氨基、二-(羟乙基)-氨基、羟基、低烷氧基、烯丙氧基、甲氧基低烷氧基、氰基、羧酰胺基、羧基、低烷氧基羧酰基、羟甲基、低烷氧甲基、卤甲基、氨基甲基、低酰氨基甲基、二-(低烷基)-氨基甲基、吡咯烷基甲基、哌啶基甲基、二-(羟乙基)-氨基甲基、吗啉基甲基、哌嗪基甲基、4-低酰基哌嗪基甲基、4-低烷基哌嗪基甲基、低烷基、低烯基、2-氰乙基、2-(低烷氧羰基)-乙基、2-羧乙基、2-羟乙基、苯基低烷基和苯基的单价或二价取代基，其中苯基基团可选地取代1或2个羟基或甲氧基，或来自氧或硫；其光学活性形式和其外消旋混合物，以及其药理兼容的盐。本发明还提供了制备这些化合物的方法和含有它们的制药组合物。
• Cardioactive pyrazole and imidazole aryloxypropanolamines
  申请人：Boehringer Mannheim GmbH

  公开号：US04608383A1

  公开（公告）日：1986-08-26

  The present invention provides aryloxypropanolamines of the general formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are hydrogen or halogen atoms or lower alkyl, cyano, carboxamide, hydroxyl, lower acyloxy, lower alkoxy, lower alkenyloxy or aryl lower alkoxy radicals, R.sub.5 and R.sub.6, which may be the same or different, are hydrogen atoms or lower alkyl radicals, X is a straight or branched alkylene chain containing 2 to 6 carbon atoms, A is a mono-, bi- or tricyclic heteroaromatic or hydroheteroaromatic radical or, when at least one of the symbols R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is other than a hydrogen atom, may also be a phenyl radical, with the proviso that when A is a uracil-6-yl radical, the 5-position of the uracil moiety does not contain a hydrogen atom, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11, which may be the same or different, are mono- or divalent substituents selected from hydrogen, halogen, notro, hydraxylamino, amino, lower acylamino, lower alkylamino, di-(lower alkyl)-amino, hydroxyethylamino, di-(hydroxyethyl)-amino, hydroxyl, lower alkoxy, allyloxy, methoxy lower alkoxy, cyano, carboxamido, carboxy, lower alkoxycarbonyl, hydroxymethyl, lower alkoxymethyl, halomethyl, aminomethyl, lower acylaminomethyl, halomethyl, aminomethyl, lower acylaminomethyl, di(lower alkyl)-aminomethyl, pyrrolidinomethyl, piperidinomethyl, di-(hydroxyethyl)-amino, hydroxyl, lower alkoxy, allyloxy, methoxy lower alkoxy, cyano, carboxamido, carboxy, lower alkoxycarbonyl, hydroxymethyl, lower alkoxymethyl, halomethyl, aminomethyl, lower acyaminomethyl, di-(lower alkyl)-aminomethyl, pyrrolidinomethyl, piperidinomethyl, di-(hydroxyethyl)-aminomethyl, morpholinomethyl, piperazinomethyl, 4-lower acylpiperazinomethyl, 4-lower alkylpiperazinomethyl, lower alkyl, lower alkenyl, 2-cyanoethyl, 2-hydroxyethyl, phenyl lower alkyl and phenyl, the phenyl radicals being optionally substituted with 1 or 2 hydroxyl or methoxy radicals, or from oxygen or sulphur; the optically-active forms and the racemic mixtures thereof, and the pharmacologically compatible salts thereof. The present invention also provides processes for the preparation of these compounds and pharmaceutical compositions containing them. These compounds are useful for the prophylaxis and combatting of cardiac and circulatory diseases.

  本发明提供了一般式为：##STR1## 的芳氧基丙醇胺，其中R.sub.1、R.sub.2、R.sub.3和R.sub.4，可以相同或不同，是氢或卤素原子或低烷基、氰基、羧酰胺、羟基、低酰氧基、低烷氧基、低烯烃氧基或芳基低烷氧基基团，R.sub.5和R.sub.6，可以相同或不同，是氢原子或低烷基基团，X是含有2至6个碳原子的直链或支链烷基链，A是单环、双环或三环杂芳基或水杂芳基基团，或者当R.sub.1、R.sub.2、R.sub.3和R.sub.4中至少有一个符号不是氢原子时，也可以是苯基基团，但前提是当A是尿嘧啶-6-基团时，尿嘧啶基团的5位不含有氢原子，R.sub.7、R.sub.8、R.sub.9、R.sub.10和R.sub.11，可以相同或不同，是从氢、卤素、硝基、羟基氨基、氨基、低酰胺基、低烷基氨基、二（低烷基）氨基、羟乙基氨基、二（羟乙基）氨基、羟基、低烷氧基、烯丙氧基、甲氧基低烷氧基、氰基、羧酰胺基、羧基、低烷氧羰基、羟甲基、低烷氧甲基、卤甲基、氨基甲基、低酰胺基甲基、卤甲基、氨基甲基、低酰胺基甲基、二（低烷基）氨基甲基、吡咯烷基甲基、吡啶烷基甲基、二（羟乙基）氨基甲基、羟基、低烷氧基、烯丙氧基、甲氧基低烷氧基、氰基、羧酰胺基、羧基、低烷氧羰基、羟甲基、低烷氧甲基、卤甲基、氨基甲基、低酰胺基甲基、二（低烷基）氨基甲基、吡咯啉基甲基、哌嗪基甲基、4-低酰基哌嗪基甲基、4-低烷基哌嗪基甲基、低烷基、低烯基、2-氰基乙基、2-羟基乙基、苯基低烷基和苯基的单价或二价取代基，其中苯基基团可以选择性地取代1或2个羟基或甲氧基基团，或者从氧或硫；其光学活性形式和混合物，以及其药理学上相容的盐。本发明还提供了制备这些化合物的方法和含有它们的制药组合物。这些化合物对于预防和治疗心脏和循环系统疾病是有用的。